Phosphate compositions with a low aluminum content
The present disclosure provides compositions comprising phosphate salts having low levels of aluminum, as well as other elemental impurities. In general, phosphate salts compositions disclosed herein are liquid compositions (e.g., admixtures, solutions) comprising in situ formed phosphate salts, a pharmaceutically acceptable carrier, and less than about 250 μg/L of aluminum. Phosphate salts solutions disclosed herein are stable over time (e.g., the amount of total phosphorus and/or the ratio of phosphate salts and/or the level of aluminum does not substantially vary, and the compositions remain free of visible particulate matter). The compositions do not require storage at less than ambient (room) temperature, i.e., no refrigeration is needed. Also provided herein are methods and systems for preparing in situ phosphate salts compositions, and methods of using phosphate salt compositions to provide phosphorous to individuals in need thereof.
1. A solution for parenteral administration comprising potassium phosphate salts in an amount that provides to the solution about 3 millimoles/mL total phosphorus and a pharmaceutically acceptable carrier in a sealed container, wherein the solution contains less than 250 μg/L of aluminum after storage for 12 months at 25° C. and 40% relative humidity, and wherein the phosphate salts are formed in situ by reacting phosphoric acid with a cationic base.
2. The solution of claim 1 , wherein the solution contains less than 200 μg/L of aluminum after storage for 12 months at 25° C. and 40% relative humidity in a sealed container.
3. The solution of claim 2 , wherein the solution contains less than 100 μg/L of aluminum after storage for 12 months at 25° C. and 40% relative humidity in a sealed container.
4. The solution of claim 1 , wherein the pharmaceutically acceptable carrier is Water for Injection, saline, or a dextrose solution.
5. The solution of claim 1 , wherein the phosphate salts are formed in situ by reacting phosphoric acid with potassium hydroxide.
6. The solution of 1 , wherein the phosphate salts are monobasic potassium phosphate and dibasic potassium phosphate.
7. The solution of claim 1 , wherein the solution has a pH of about pH 6 to about pH 8.
8. The solution of claim 1 , wherein the solution has a pH of about pH 6.5 to about pH 7.5 or a pH of about pH 6.2 to pH 6.8.
9. A solution for parenteral administration comprising potassium phosphate salts in a pharmaceutically acceptable carrier, wherein the solution contains less than about 250 μg/L of aluminum and has no more than 0.00309 millimoles of aluminum for every mole of phosphorus provided by the potassium phosphate salts, wherein the phosphate salts are formed in situ by reacting phosphoric acid with a cationic base.
10. The solution of claim 9 , wherein the solution contains less than about 250 μg/L of aluminum and has no more than 0.00309 millimoles of aluminum for every mole of phosphorus in the solution.
11. The solution of claim 9 , wherein the solution contains less than about 200 μg/L of aluminum.
12. The solution of claim 9 , wherein the solution contains less than about 100 μg/L of aluminum.
13. The solution of claim 9 , wherein the pharmaceutically acceptable carrier is Water for Injection, saline, or a dextrose solution.
14. The solution of claim 9 , wherein the phosphate salts are formed in situ by reacting phosphoric acid with potassium hydroxide.
15. The solution of claim 9 , wherein the phosphate salts are monobasic potassium phosphate and dibasic potassium phosphate.
16. The solution of claim 15 , wherein the solution has a pH of about pH 6 to about pH 8.
17. The solution of claim 16 , wherein the solution has a pH of about pH 6.5 to about pH 7.5 or a pH of about pH 6.2 to pH 6.8.
18. The solution of claim 9 , wherein the solution contains less than 250 μg/L of aluminum after storage for 12 months at 25° C. and 40% relative humidity in a sealed container.